Three-year follow-up of outcomes with KTE-X19 in patients with relapsed/refractory mantle cell lymphoma in ZUMA-2.
Authors: Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron Alyce Jacobson, Brian T Hill, John Timmerman, Houston Holmes, Ian W. Flinn, David Bernard Miklos, John M. Pagel, Marie José Kersten, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine Shen, Rubina Siddiqi, Ioana Kloos, Patrick Michael Reagan
Journal: Journal of Clinical Oncology (2022)

7518 Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL). In ZUMA-2, a 93% objective response rate (ORR; 67% complete response [CR] rate) was reported with KTE-X19 in pts with R/R MCL (median follow-up: 12.3 mo; 60 efficacy-evaluable pts; Wang et al. N Engl J Med. 2020). Here, we present updated outcomes with 2 years of additional follow-up. Methods: Adult pts (≥18 years) with R/R MCL underwent leukapheresis and conditioning chemotherapy followed by a single infusion of KTE-X19. Minimal residual disease (MRD) was an exploratory endpoint (sensitivity 10-5) evaluated in peripheral blood using next-generation sequencing. Updated results are reported for all 68 treated pts. Results: After 35.6 mo median follow-up, the ORR (CR + partial response) was 91% (95% CI, 81.8-96.7), with a 68% CR rate (95% CI, 55.2-78.5). The median duration of response (DOR) was 28.2 mo (95% CI, 13.5-47.1), with 25 of 68 treated pts (37%) still in ongoing response (all CR) at data cutoff. Late relapse &gt; 24 mo post-infusion was infrequent (n = 3). The medians for progression-free survival (PFS) and overall survival (OS) were 25.8 mo (95% CI, 9.6-47.6) and 46.6 mo (95% CI, 24.9-not estimable), respectively. MRD was analyzed in 29 pts total; 24 of 29 were MRD-negative at mo 1, and 15 of 19 with available data were MRD-negative at mo 6. At data cutoff, the medians for DOR, PFS, and OS in the 15 MRD-negative pts were all not reached, vs 6.1, 7.1, and 27.0 mo, in the 4 MRD-positive pts, respectively. MRD-negative status at mo 1, 3, and 6 was associated with durable response, with 55%, 71%, and 69% of MRD-negative pts at those timepoints remaining in ongoing CR at data cutoff. Circulating tumor DNA analysis of MRD at mo 3 and 6 was predictive of relapse (AUC 0.80 and 0.75, respectively). No new safety signals were observed. Only 3% of treatment-emergent adverse events (AEs) of interest occurred since the primary report. The most frequent Grade ≥3 AE was neutropenia (1 [1%] Grade 3; 7 [10%] Grade 4). Two pts had KTE-X19-related Grade 3 serious infections: pneumonia and upper respiratory tract infection (n = 1); influenza (n = 1). There were no new cytokine release syndrome AEs and 1 new serious neurologic AE of Grade 3 encephalopathy (13.0 mo post-infusion) that was considered not related to study treatment. Three new Grade 5 AEs occurred, none of which were considered related to study treatment: Salmonella bacteremia (24.9 mo post-infusion), myelodysplastic syndrome (25.2 mo post-infusion), and acute myeloid leukemia (37.5 mo post-infusion). Conclusions: These data represent the longest follow-up of CAR T-cell therapy in pts with MCL to date and suggest that KTE-X19 induces durable long-term responses with manageable safety and low late relapse potential in R/R MCL. Clinical trial information: NCT02601313.